None listed
Conditions
Brief summary
The purpose of this study is to assess how safe and effective elranatamab is in treating newly diagnosed systemic AL amyloidosis. You may be eligible to participate if you are 18 years of age or older, have been recently diagnosed with this condition, and have not yet received any treatment. If you join the study, you will be given elranatamab as an injection under the skin for up to 6 treatment cycles, with each cycle lasting approximately 28 days. Throughout the study, your health will be carefully monitored to assess how you respond to the treatment and to identify any potential side effects. Following completion of treatment, you will attend follow-up visits every three months for up to five years. The purpose of this study is to determine whether elranatamab can slow or stop the progression of the disease, and whether it's safe to have it.
Interventions
This is a phase II single arm clinical study.
Elrantamab will be administered by hospital staff and is given subcutaneously. Each treatment cycle is 28 days and maximum number of treatment cycles is 6. Treatment cycles will be back to back. There is no treatment break unless due to side effects.
The dose schedule is:
-Cycle 1 Day 1 - 12mg
-Cycle 1 Day 4 - 32mg
-Cycle 1 Day 8: 76mg
-Cycle 1 Day 15 - 76mg
-Cycle 1 Day 22 - 76mg
-Cycle 2 - 76mg weekly
- From Cycle 3 onwards, dosing frequency wil
This is a phase II single arm clinical study. Elrantamab will be administered by hospital staff and is given subcutaneously. Each treatment cycle is 28 days and maximum number of treatment cycles is 6. Treatment cycles will be back to back. There is no treatment break unless due to side effects. The dose schedule is: -Cycle 1 Day 1 - 12mg -Cycle 1 Day 4 - 32mg -Cycle 1 Day 8: 76mg -Cycle 1 Day 15 - 76mg -Cycle 1 Day 22 - 76mg -Cycle 2 - 76mg weekly - From Cycle 3 onwards, dosing frequency will be guided by disease response. If a participant achieves a Complete Response (CR) from the blood tests at Cycle 3 Day 1 or prior, elranatamab will be given every 4 weeks (76mg) till the end of Cycle 6. For participants haven't achieved CR at Cycle 3 Day 1, treatment will be given every 2 weeks (76mg) till reassessed at Cycle 5 Day 1. If participant achieves CR at Cycle 5 Day 1, treatment will be given every 4 weeks (76mg) till the end of Cycle 6. Otherwise, participant will continue with 76mg every 2 weeks till the end of Cycle 6. Adherence to the intervention will be closely monitored by study staff. Elranatamab is administered subcutaneously by hospital staff at scheduled study visits, ensuring that all doses are given under direct supervision. Administration dates, doses, and any missed, delayed, interrupted, or discontinued treatments will be documented in the participant's study records and case report forms. Compliance with the protocol-specified dosing schedule will be reviewed throughout the study, and any deviations will be recorded and assessed by the study team.
Sponsors
Australasian Myeloma Research Consortium
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1.At least 18 years old. 2.Capable of giving consent 3.No contraindication to the use of the study drug and able to comply with trial requirements. 4.Histopathological diagnosis of AL amyloidosis based on detection by polarizing light microscopy of green bi-refringent material in Congo red-stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance. 5.Measurable disease of amyloid light chain amyloidosis as defined by at least ONE of the following: o Serum M-protein at least 5g/L by protein electrophoresis (routine serum protein electrophoresis and immunofixation (IFE) performed at a central laboratory, this cannot be an IgM M-protein), o Serum free light chain at least 50 mg/L with an abnormal kappa: lambda ratio or the difference between involved and uninvolved free light chains (dFLC) at least 50 mg/ L. o Note: Measurable disease by urine Bence-Jones proteinuria or IgM M-protein is not sufficient for study enrolment. 6.One or more organs impacted by AL amyloidosis according to consensus guidelines 7.ECOG Performance Status 0-2. 8.Clinical laboratory values meeting the following criteria during the Screening Phase: o Absolute neutrophil count greater than or equal to 1.0 × 109/L; o Haemoglobin level greater than or equal to80 g/L; red blood cell transfusion allowed until 7 days before registration. o Platelet count greater than or equal to75,000/µL if less than 50% of BM nucleated cells are plasma cells, or greater than or equal to 50,000/µL if at least 50% of BM nucleated cells are plasma cells (transfusion support is permitted if completed at least 7 days prior to eligibility sample collection and at least 7 days prior to planned start of dosing) o Alanine aminotransferase level (ALT) less than or equal to 2.5 times the ULN. o Aspartate aminotransferase (AST) less than or equal to 2.5 times the ULN. o Total bilirubin level less than or equal to 1.5 × ULN except for subjects with Gilbert syndrome, in which case direct bilirubin less than or equal to 2 × ULN. o Estimated glomerular filtration rate (eGFR) greater than or equal to 20 mL/min/1.73 m2. 9.Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. Contraception must begin 4 weeks prior to dosing and continue for 4 months after discontinuation of elranatamab. During this same period a woman must agree not to donate eggs for the purposes of assisted reproduction. 10.Woman of childbearing potential must have a negative pregnancy test result within 72 hours of treatment initiation. 11.A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control during and for 4 months after discontinuation of elranatamab. During this same period all men must not donate sperm.
Exclusion criteria
1.Prior therapy for AL amyloidosis or multiple myeloma, except for 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to treatment initiation. 2.Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, anaemia, greater than or equal to 60% plasma cells in the bone marrow or hypercalcemia. IF the only myeloma defining feature is an involved-to-uninvolved free light chain ratio greater than or equal to 100:1, that is permitted. 3. Patients with AL amyloidosis associated with a clonal lymphoplasmacytic or B-cell population. 4. Evidence of significant cardiovascular conditions. 5.Planned stem cell collection or stem cell transplant during the first 6-months of therapy 6. Any form of non-AL amyloidosis, including wild type or mutated (ATTR) amyloidosis. 7. Known allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, or their excipients, or known sensitivity to mammalian-derived products. 8. Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) 2 years. o Stage 1 prostate cancer that does not require treatment. o Any other cancer from which the subject has been disease-free for > 2 years. 13. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. 14.Participation in other clinical trials for the treatment of AL amyloidosis, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
Outcome results
None listed